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Departments of
*
Immunohematology and Blood Transfusion,
Human and Clinical Genetics, and
Pathology, Leiden University Medical Center, Leiden, The Netherlands; and
Institut National de la Santé et de la Recherche Médicale, Unité 520, Section Recherche, Institut Curie, Paris, France
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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R-mediated
internalization of Ag-Ab immune complexes (ICs) can induce maturation
of DCs. In this study, we show that IC-induced DC maturation in vitro
enables DCs to prime peptide-specific CD8+ CTLs in vivo,
independently of CD4+ Th cells. Importantly,
OVA/anti-OVA IC-treated DCs not only primed CD8+ CTLs
to an exogenously loaded peptide nonrelated to OVA, but also
efficiently primed CTLs against the dominant CTL epitope derived from
the OVA Ag present in the ICs. Our studies show that ICs fulfill a dual
role in priming of CD8+ CTL responses to exogenous Ags:
enhancement of Ag uptake by DCs and activation of DCs, resulting in
"license to kill." These findings indicate that the presence of
specific Abs can crucially affect the induction of cytotoxic cellular
responses. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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DCs internalize exogenous Ags by fluid-phase pinocytosis or by
receptor-mediated endocytosis. Peptides derived from exogenous Ags are
presented efficiently in MHC class II molecules (5).
Although MHC class I molecules are generally complexed with peptides
derived from cytosolic Ags, exogenous Ags can be processed and
presented in MHC class I molecules after internalization (6, 7). Class I-restricted presentation of Ags internalized by
fluid-phase pinocytosis is very inefficient and requires high Ag
concentrations. Presentation of exogenous Ags in MHC class I can be
improved by complexing Ags to beads (8), by providing Ags
in bacteria (9), or by administering Ags in apoptotic
cells (10). Furthermore, DCs express several receptors
that facilitate the internalization and presentation of Ags, including
C-type lectin receptors such as the mannose receptor (5)
and DEC205 (11), as well as receptors for the Fc domain of
Igs (FcR and Fc
R, which bind the Fc domain of IgG and IgE,
respectively (12)). FcRs are expressed on most cells of
the hemopoietic lineages, including DCs, and play a pivotal role in
linking the humoral and cellular arms of the immune response. Ag-IgG
complexes (immune complexes (ICs)), which bind to and cross-link
FcRs, mediate a variety of responses in vitro ranging from
phagocytosis to Ab-mediated cellular cytotoxicity. FcR-mediated
internalization of ICs by DCs is associated with enhanced presentation
of both MHC class I- and MHC class II-binding peptides derived from the
Ag present in the ICs and leads to activation of the DCs
(13, 14, 15). The in vivo contribution of FcRs and ICs to
CD4+ Th cell function has been studied recently
(16). In this study, mice lacking the FcRI-,
FcRIII-, and FcRI-associated -chain, which is required for
signaling and the cell surface expression of these receptors, showed
decreased delayed-type hypersensitivity responsiveness and defective Th
cell responses to a model Ag.
In this study, we have shown the in vivo CTL-priming capacity of IC-treated DCs. IC-mediated activation of DCs enables these cells to efficiently prime CD8+ CTL responses both against an exogenously loaded peptide and against endogenously processed peptide from the Ag present in the ICs. These findings underscore the relevance of cross talk through DCs between the B and T cell compartments of the immune system.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Female C57BL/6 (B6; H-2b) mice were obtained from IFFA Credo (Paris, France). Mice were maintained under specific pathogen-free conditions and used at 6–10 wk of age.
Cell lines and reagents
Human adenovirus type 5 (Ad5) E1-transformed B6 mouse embryo
cells (MECs) and B6 MECs transfected with murine CD80 (B7.1),
H-2Kb, and a construct expressing an endoplasmic
reticulum targeting signal sequence, followed by the
OVA257–264 CTL epitope SIINFEKL (SigSIINFEKL),
were generated as described (17, 18). B3Z is a T cell
hybridoma specific for SIINFEKL in H-2Kb, which
carries a 
-galactosidase construct driven by NF-AT elements from the
IL-2 promotor (19). Cell lines were cultured in IMDM
(BioWhittaker, Verviers, Belgium) supplemented with 8%
heat-inactivated FCS (Greiner, Alphen, The Netherlands), 100 IU/ml
penicillin, 2 mM L-glutamine, and 20 µM 2-ME. D1 cell
line, a long-term growth factor-dependent immature splenic DC line
derived from B6 mice, was kindly provided by P.
Ricciardi-Castagnoli (University of Milano-Bicocca, Milan,
Italy) and cultured as described (20). Bone marrow-derived
(BM) primary DC cultures (BM DCs) were generated as described
(21). Both floating and adherent DCs (detached using 2 mM
EDTA) were collected and used. LPS of Escherichia coli
(serotype 026:B6) was purchased from Sigma-Aldrich (St. Louis, MO).
Synthetic peptides used were: OVA257–264,
SIINFEKL; vesicular stomatitis virus nucleoprotein (VSV
NP52–59), RGYVYQGL; Ad5
E1A234–243, SGPSNTPPEI; and human papillomavirus
type 16 E749–57, RAHYNIVTF.
Abs and cell surface immunofluorescence
The following Abs were purchased from BD PharMingen (San Diego,
CA): FITC-coupled anti-CD86/B7.2 Ab (GL1), FITC-coupled
anti-CD8 Ab (Ly-3.2), allophycocyanin-coupled
anti-CD8
Ab (Ly-2). PE-conjugated Ad5
E1A234–243-loaded H-2Db
and PE-conjugated SIINFEKL-loaded H-2Kb tetramers
were prepared as described (22, 23, 24). Ad5
E1A234–243-loaded
H-2Db tetramers were kindly provided by T.
Schumacher (NKI, Amsterdam, The Netherlands). Staining for
H-2Db-E1A234–243
tetrameric complexes and anti-CD8-allophycocyanin was conducted
at 37°C for 15 min. For H-2Kb-SIINFEKL
tetrameric complexes, cells were incubated for 30 min at room
temperature with tetrameric complexes, washed, and incubated for
another 30 min at room temperature with FITC-coupled anti-CD8
Ab. Stained cells were analyzed using a FACScan flow cytometer equipped
with CellQuest software (BD Biosciences, Mountain View, CA).
Incubation with ICs, MHC class I-restricted Ag presentation assay, and IL-12 ELISA
ICs were preformed by incubating soluble OVA (grade V;
Sigma-Aldrich) with 25 µg/ml polyclonal OVA-specific rabbit
IgG (rIgGOVA; Sigma-Aldrich) for 30 min at 37°C in 96-well
flat-bottom plates. As a control, soluble OVA was preincubated with 25
µg/ml control rabbit IgG. A total of 5 x
104 D1 cells/well was added and incubated for
24 h at 37°C. Supernatants were harvested, and 5 x
104 B3Z cells/well were added to the D1 cells and
incubated for another 24 h at 37°C. Presentation of SIINFEKL in
H-2Kb was detected by activation of B3Z cells,
measured by a colorimetric assay using chlorophenol
red--D-galactopyranoside as substrate to detect
lacZ activity in B3Z lysates. Harvested supernatants were
tested for IL-12 p40/p70 content using a standard sandwich ELISA.
Coating Ab: rat anti-mouse IL-12 p40/p70 mAb (clone C15.6; BD
PharMingen). Detection Ab: biotinylated rat anti-mouse IL-12
p40/p70 mAb (clone C17.8; BD PharMingen). Streptavidin-HRP and ABTS
(Sigma-Aldrich) were used as enzyme and substrate, respectively.
Uptake of OVA-FITC and confocal microscopy
OVA-ICs were preformed as described in the previous paragraph, using FITC-labeled OVA (Molecular Probes, Leiden, The Netherlands), in 96-well plates. Fifty thousand D1 cells were added to wells containing OVA-ICs or soluble OVA with control rabbit IgG and incubated for different time periods at 37°C. Cells were harvested and resuspended in the absence or presence of 0.4% (w/v) trypan blue (Sigma-Aldrich), which quenches extracellular, but not intracellular, fluorescence (25). Flow cytometry was performed with FACScan. For analysis by confocal microscopy, D1 cells were grown on 3-cm petri dishes for 2 days and then incubated with OVA-ICs or OVA with control rabbit IgG for 1 h at 37°C. After washing, cells were fixed by incubation with 1% paraformaldehyde for 15 min, followed by blocking with 0.2 M glycine. Cells were analyzed by confocal microscopy (Carl Zeiss microscope; Zeiss, Oberkochen, Germany). Analysis of the cells by Z-scan analysis, showing images of optical slices from the top to the bottom of the cells, was performed using LSM 510 Image browser software.
Induction of CTL responses in vivo
To induce CTL responses in vivo against exogenously loaded Ad5 E1A234–243 (SGPSNTPPEI) or against the endogenously processed MHC class I-binding peptide OVA257–264 (SIINFEKL) derived from the OVA protein Ag present in the ICs, D1 cells or BM DCs were incubated for 48 h with OVA-ICs, with soluble OVA alone or in the presence of control rabbit IgG, or 10 µg/ml LPS, followed by loading with 1 µg/ml Ad5 E1A234–243 for 2 h at 37°C. After five times washing, 106 D1 cells were injected i.v. in B6 mice in PBS with 0.5% BSA. Mice were depleted of CD4+ cells by i.p. injection of 100 µg purified anti-CD4 Ab GK1.5 in PBS at days 5, 3, and 1 before, and at days 1 and 7 after injection of D1 cells. CD4+ cell populations were below detection level by flow cytometry. Depletion was performed to prevent endogenous CD4+ Th cells from activating the D1 cells in vivo (our unpublished results). After 10 days, spleen cells were used for detection of responses by direct ex vivo staining with tetrameric complexes. In addition, spleen cells were cocultured (5 x 106 cells/well) with irradiated (10,000 rad) Ad5-transformed MECs (5 x 105/well) to restimulate responses to the exogenously loaded Ad5 peptide or with irradiated (10,000 rad) B7.1-, H-2Kb-, and SigSIINFEKL-transfected MECs (5 x 105/well) to restimulate responses to the SIINFEKL peptide, in 1.5-ml cultures in 24-well plates in the absence of additional cytokines. After 7 days, lymphocyte cultures were tested for staining with tetrameric complexes and for cytotoxicity against Eu3+-labeled target cells loaded with Ad5 E1A234–243 or control H-2Db-binding peptide (human papillomavirus type 16 E749–57) or with SIINFEKL or control H-2Kb-binding peptide (VSV NP52–59).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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To establish and optimize the treatment of DCs with ICs in our
laboratory, the efficiency of MHC class I-restricted Ag presentation of
OVA-derived epitopes upon incubation of the well-established immature
murine DC line D1 (20) with OVA-ICs was analyzed. D1 cells
were incubated with OVA-ICs containing titrated amounts of OVA protein
and a fixed concentration of OVA-specific rabbit IgG (rIgGOVA).
After 24 h, presentation of H-2Kb-restricted
OVA257–264 CTL epitope (SIINFEKL) was analyzed
by measuring the activation of B3Z T cell hybridoma cells. OVA-ICs
induced very efficient presentation of the SIINFEKL epitope. Optimal IC
formation was achieved at about 1 µg/ml OVA at a fixed Ab
concentration of 25 µg/ml (Fig. 1
A). In contrast, detectable
processing and presentation of SIINFEKL by D1 cells after incubation
with soluble OVA or OVA with control rabbit IgG were only observed at
OVA concentrations of 30 µg/ml or higher. At higher concentrations of
OVA, no optimal IC formation takes place (see below); therefore, the
level of T cell activation follows the curve of soluble OVA protein
above 10 µg/ml.
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B) and increased surface expression of
CD86 (B7.2) (Fig. 1C), CD40, and MHC class I
(Kb) (data not shown) were induced by OVA-ICs,
but not by rIgGOVA alone, soluble OVA, or OVA with control rabbit
IgG. These data show that ICs induce functional activation of DCs by
up-regulation of relevant surface molecules, induction of IL-12
production, as well as improved efficiency of MHC class I-restricted Ag
presentation. Activation of DCs is not sufficient to improve MHC class I-restricted Ag presentation
ICs can activate DCs. To test the possibility that DC activation
as such enhances presentation of OVA-derived epitopes, we incubated D1
cells with soluble OVA protein in the presence or absence of the potent
DC-activating compound LPS. D1 cells incubated with soluble OVA and
stimulated with LPS did not exhibit improved presentation of SIINFEKL
to B3Z T cell hybridoma cells. In contrast, OVA-ICs strongly improved
presentation of this CTL epitope (Fig. 2A). IL-12 production by D1
cells was induced by both LPS and OVA-ICs (Fig. 2B). In the
case of LPS treatment, IL-12 levels were independent of the
concentration of OVA used, but IL-12 levels reached an optimum at about
1 µg/ml OVA for OVA-ICs (Fig. 1B and data not shown).
Thus, as both LPS and ICs induce DC activation, but only ICs enhance Ag
presentation, activation of the DCs by itself is not sufficient to
enhance MHC class I-restricted presentation of peptides derived from
exogenous Ags.
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Enhanced MHC class I-restricted presentation of Ag present in ICs
can be due to more efficient internalization of complexed Ag, mediated
by FcRs expressed on DCs, compared with soluble Ag. To investigate
this, D1 cells were incubated with 1 µg/ml OVA-FITC in ICs, 1 µg/ml
OVA-FITC with control rabbit IgG, or 100 µg/ml soluble OVA. After
different incubation times, cells were harvested and resuspended in the
absence or presence of trypan blue. Trypan blue quenches extracellular,
but not intracellular, fluorescence (25). D1 cells
incubated with OVA-FITC-ICs were strongly fluorescent, already after
10-min incubation (Fig. 3A).
At this time point, one-quarter of the fluorescence was not quenched by
trypan blue; therefore, a major portion of the OVA appeared to be
internalized. After 3 h, most of the fluorescent OVA was
internalized. This indicates that uptake of OVA complexed to Abs is
very efficient. Soluble OVA was taken up as well, but far less
efficiently. Uptake could only be observed at high concentrations of
OVA (100 µg/ml) in contrast to 1 µg/ml OVA, which is the
corresponding concentration used in ICs (Fig. 3B). Soluble
OVA-FITC could not be quenched by trypan blue, indicating that there is
hardly any binding to the cell surface. FACS profiles of cells
incubated for 30 min with OVA-FITC-ICs, OVA-FITC with control rabbit
IgG, or a high concentration of soluble OVA-FITC are shown in Fig. 3C. Confocal microscopy analysis of D1 cells incubated with
1 µg/ml OVA-FITC in ICs or 1 µg/ml soluble OVA-FITC showed strongly
fluorescent cells for ICs (Fig. 4A), but not for soluble OVA
(Fig. 4B). Strongly fluorescent D1 cells were observed,
however, when 1 mg/ml soluble OVA was used (Fig. 4C). Z-scan
analysis of optical slices from the top to the bottom of the cells
indicated that the OVA-FITC in ICs was indeed largely internalized
(data not shown). Thus, the enhanced Ag presentation observed after
incubation of DCs with ICs compared with soluble Ag is at least
partially due to increased uptake of Ag.
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We have recently shown that activation of D1 cells by LPS
treatment or CD40 triggering induces efficient
CD8+ CTL-priming capacity in vivo
(4). To investigate whether IC-mediated activation of D1
cells reflects functional activation and leads to efficient CTL priming
in vivo, D1 cells were treated with LPS, soluble OVA, OVA with control
rabbit IgG, or OVA-ICs. Cells were washed, exogenously loaded with an
Ad5 CTL epitope, and injected i.v. into mice depleted for
CD4+ cells. Ten days after immunization, spleens
were harvested and splenocytes were analyzed directly ex vivo for the
presence of Ad5-specific CD8+ cells by staining
with PE-conjugated
H-2Db-E1A234–243
tetrameric complexes. Both LPS- and OVA-IC-activated D1 cells induced
considerable amounts of CD8+ cell staining with
tetrameric complexes in 6 of 10 and 13 of 16 mice, respectively. In
contrast, none of the mice injected with peptide-loaded D1 cells that
were preincubated with soluble OVA or OVA with control rabbit IgG had
significant numbers of CD8+ cells staining with
tetrameric complexes (Fig. 5). Staining
of splenocytes with tetrameric complexes 7 days after in vitro
restimulation with Ad5-transformed stimulator cells showed similar
results, although the percentages of tetramer-positive cells were
higher due to the restimulation (data not shown). Measurement of
Ad5-specific cytotoxic activities of these bulk cultures paralleled the
results obtained by staining with tetrameric complexes (data not
shown). Thus, IC-induced activation of D1 cells enables these cells to
prime efficient CTL responses in vivo in mice depleted for
CD4+ cells, and therefore bypasses
CD4+ T cell help.
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Incubation of D1 cells with OVA-ICs results in up-regulation of
the expression of costimulatory and MHC molecules, induction of IL-12
production, increased OVA uptake, and efficient MHC class I-restricted
presentation of OVA-derived peptides. We investigated whether
OVA-IC-activated D1 cells are capable of inducing OVA-specific CTLs in
vivo. Splenocytes from the same mice described in the previous
paragraph, harvested 10 days after immunization, were analyzed directly
ex vivo for the presence of OVA-specific CD8+
cells by staining with H-2Kb-SIINFEKL tetrameric
complexes. In contrast to the Ad5-specific CTLs, staining of
splenocytes directly ex vivo did not show significant staining of
CD8+ cells for tetrameric complexes in any of the
mice (data not shown). However, 7 days after in vitro restimulation
with Kb-SIINFEKL-expressing stimulator cells,
cultures showed high numbers of CD8+ cells
staining with tetrameric complexes in mice injected with D1 cells
incubated with OVA-ICs. No detectable staining of
CD8+ cells for tetrameric complexes was detected
in cultures from mice injected with D1 cells incubated with soluble
OVA, OVA with control rabbit IgG, or LPS (Fig. 6A). D1 cells incubated with
soluble OVA and LPS did not induce CD8+ cell
staining with H-2Kb-SIINFEKL tetrameric
complexes. In contrast, these cells did induce
CD8+ cells specific for the exogenously loaded
peptide that stained with
H-2Db-E1A234–243
tetrameric complexes (data not shown). Furthermore, 16 of 16 mice
injected with OVA-IC-treated D1 cells showed strong CTL reactivity
against SIINFEKL (Fig. 7A)-loaded, but not against
control peptide-loaded target cells (Fig. 7B) after
restimulation in vitro. In contrast, mice that had been injected with
D1 cells incubated with LPS, soluble OVA, or OVA with control rabbit
IgG did not show any specific CTL responses against SIINFEKL-loaded
target cells (Fig. 7A).
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B). Taken together, our data show that incubation of DCs with ICs results in increased uptake and MHC class I-restricted presentation of peptides derived from the Ag present in the ICs and in maturation of the DCs. The induced activation enables DCs to prime an efficient CTL response in vivo against an exogenously loaded CTL epitope. More importantly, a strong CTL response is induced against the dominant CTL epitope derived from the Ag present in the ICs.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In the "license to kill" model (26, 27),
CD4+ Th cells activate APCs, thereby licensing
them to directly activate CTLs. Previously, we reported that LPS- and
CD40 triggering-induced maturation of DCs licenses these cells to
induce CD8+ CTL responses in vivo, in the absence
of CD4+ Th cells (4). In this study,
we show that IC-induced DC maturation enables these cells to prime
efficient peptide-specific CD8+ CTLs in vivo in
the absence of CD4+ Th cells. Furthermore, it has
been reported recently that ICs augment Ag presentation for in vivo
CD4+ Th cell responses (16). These
studies implicate that DCs play a central role in the cross talk
between humoral and cellular immune responses. DCs present MHC class I-
and II-binding peptides more efficiently when Ag is provided in the
form of ICs compared with soluble Ag (Fig. 1) (14). In
addition, IC-treated DCs are activated, which enables them to prime T
cell responses in vivo. We suggest the following model for IC-mediated
enhancement of immune responses. During an ongoing immune response, IgG
Abs may initially enhance CD4+ Th cell responses.
CD4+ Th cells are activated and improve B cell
activation, Ab production, and class switch, leading to formation of
more ICs. CD8+ CTLs may be primed more
efficiently, especially during a secondary response, when Abs are
produced quickly, leading to quicker clearance of the pathogen. In the
lymphocytic choriomeningitis virus model for example, interaction
between the cellular and humoral immune response is required for
efficient virus control (28, 29, 30). In this system, a strong
specific CD8+ CTL response initially controls the
infection. Neutralizing Abs play an important role in the long-term
control of the virus. Ab-mediated viral control is observed in
CTL-deficient mice, but virus variants emerge that escape the Ab
response. The presence of Abs may, by formation of ICs, lead to
improved CTL priming and, therefore, improved virus control, even if
the Abs have no virus-neutralizing capacity.
In this study, we show that IC-activated DCs can efficiently prime
peptide-specific CD8+ CTLs in vivo, and do so at
least as efficiently as LPS-activated DCs (Fig. 4). This might be
related to triggering of different signaling pathways by LPS and ICs.
LPS binds to and signals via Toll-like receptor 4, ultimately resulting
in activation of NF-
B (31, 32). The IgG-ICs used in
this study can bind to receptors for the Fc region of IgG Abs
(FcRs). D1 cells and fresh DCs cultured from murine bone marrow
precursors have been shown to express all three FcRs: FcRI,
FcRII, and FcRIII (15). In addition to these data,
we measured efficient binding of monomeric IgG2a to D1 cells (data not
shown). Monomeric IgG2a binds exclusively to FcRI. Furthermore, we
showed that the 2.4G2 Ab, recognizing FcRII/III, stains D1 cells,
indicating the expression on these cells of FcRII/III (data not
shown). FcRI and III are composed of a ligand-binding module and a
transducing module (the -chain), which contains immunoreceptor
tyrosine-based activation motifs (33, 34). Signal
transduction via FcRs might activate transcription factors that are
not activated by Toll-like receptor 4-mediated signal transduction,
thereby inducing additional factors playing an important role in CTL
priming in vivo.
FcRs mediate the enhanced internalization and MHC class I-restricted
presentation of peptides derived from ICs. In vitro data support that
the enhancement of MHC class I-restricted Ag presentation is FcR
mediated, as -chain-/- DCs, which lack
surface expression of FcRI, FcRIII, and FcRI, are not
activated by ICs, and do not present IC-derived MHC class I-binding
peptides more efficiently than peptides derived from soluble Ags (Ref.
15 and our unpublished data).
Different IgG subclasses have different affinities for the three
FcRs. In our studies, we have used purified OVA-specific polyclonal
rabbit IgG, which binds to all three murine FcRs
(35, 36, 37). In vivo, depending on the type of pathogen and
the local cytokine environment, different subclasses of IgG Abs are
produced. Because both activating and inhibitory FcRs exist, the
final outcome of FcR cross-linking is determined by the balance
between positive and negative signals, which depends on the IgG
subclasses locally present. We are currently investigating the relative
role of the different Ab subclasses and FcR types on the presentation
of peptides derived from ICs and the cross-priming of CTLs by DCs.
Furthermore, the affinity of the Ab and the relative location of B and
T cell epitope in the Ag have been shown to influence the efficiency of
presentation to CD4+ T cells (38, 39).
Targeting Ags to specific FcRs on APCs can markedly reduce the concentration of Ags required for a significant immunological response. Therefore, FcR targeting may be particularly useful for immunization against low dose Ag. Pretreatment of DCs with ICs in vitro, injecting preformed ICs in vivo, or aiming to vaccinate for both Ab and CTL responses are rational possibilities to design successful novel strategies for immunotherapy.
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Acknowledgments |
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Footnotes |
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2 D.H.S. and A.I.-F. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Ferry Ossendorp, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail address: f.a.ossendorp{at}LUMC.nl
4 Abbreviations used in this paper: DC, dendritic cell; Ad5, human adenovirus type 5; BM, bone marrow-derived; IC, immune complex; MEC, mouse embryo cell; VSV NP, vesicular stomatitis virus nucleoprotein.
Received for publication July 17, 2001. Accepted for publication December 31, 2001.
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. J. Exp. Med. 179:1109. receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J. Exp. Med. 189:371.This article has been cited by other articles:
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P. Schnorrer, G. M. N. Behrens, N. S. Wilson, J. L. Pooley, C. M. Smith, D. El-Sukkari, G. Davey, F. Kupresanin, M. Li, E. Maraskovsky, et al. The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture PNAS, July 11, 2006; 103(28): 10729 - 10734. [Abstract] [Full Text] [PDF]
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D. H. Schuurhuis, N. van Montfoort, A. Ioan-Facsinay, R. Jiawan, M. Camps, J. Nouta, C. J. M. Melief, J. S. Verbeek, and F. Ossendorp Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine. J. Immunol., April 15, 2006; 176(8): 4573 - 4580. [Abstract] [Full Text] [PDF]
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G. R. Rossi, M. R. Mautino, R. C. Unfer, T. M. Seregina, N. Vahanian, and C. J. Link Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing {alpha}(1,3)-Galactosyl Epitopes Cancer Res., November 15, 2005; 65(22): 10555 - 10561. [Abstract] [Full Text] [PDF]
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D. S. Pouniotis, O. Proudfoot, V. Bogdanoska, K. Scalzo, S. Kovacevic, R. L. Coppel, and M. Plebanski Selectively Impaired CD8+ but Not CD4+ T Cell Cycle Arrest during Priming as a Consequence of Dendritic Cell Interaction with Plasmodium-Infected Red Cells J. Immunol., September 15, 2005; 175(6): 3525 - 3533. [Abstract] [Full Text] [PDF]
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